PMID- 30896438
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20201125
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 24
IP  - 4
DP  - 2019
TI  - Effect of rifabutin on the pharmacokinetics of oral cabotegravir in healthy 
      subjects.
PG  - 301-308
LID - 10.3851/IMP3306 [doi]
AB  - BACKGROUND: Cabotegravir (CAB) is an integrase strand transfer inhibitor in 
      development as a long-acting injectable formulation, with an oral formulation 
      used during a safety lead-in period. Tuberculosis (TB)-HIV coinfection is common, 
      often requiring simultaneous treatment. Rifabutin (RBT) is an alternative 
      antimycobacterial agent for TB and a moderate inducer of cytochrome P450 and 
      UDP-glucuronosyltransferase isoenzymes. This study evaluated the impact of RBT on 
      the pharmacokinetics (PK) of oral CAB. METHODS: In this Phase I, single-centre, 
      open-label, two-period, fixed-sequence, drug interaction study, subjects received 
      oral CAB 30 mg once daily for 14 days in period 1, and oral CAB plus RBT 300 mg 
      once daily for 14 days in period 2. Serial PK sampling was performed on days 14 
      and 28. Geometric least squares (GLS) mean ratios with associated 90% CIs were 
      calculated to compare CAB noncompartmental PK parameters following CAB+RBT versus 
      CAB alone. Safety was also assessed. RESULTS: A total of 15 male subjects were 
      enrolled and 12 completed all treatments. Comparing CAB+RBT with CAB alone, the 
      GLS mean ratios (90% CIs) for CAB area under the concentration-time curve from 
      time zero to the end of the dosing interval (AUC(0-tau)), maximum observed plasma 
      concentration (C(max)) and concentration at the end of the dosing interval (C(tau)) 
      were 0.79 (0.74, 0.83), 0.83 (0.76, 0.90) and 0.74 (0.70, 0.78), respectively. 11 
      subjects reported 24 adverse events (AEs); 22 were reported with CAB+RBT (3 
      drug-related) and 2 with CAB alone (not drug-related). All AEs resolved by study 
      end. CONCLUSIONS: RBT had a modest impact on plasma CAB exposure following oral 
      coadministration, resulting in overall plasma CAB trough exposures above the 10 
      mg oral dose shown to maintain viral suppression in HIV-1-infected subjects. Oral 
      CAB can be coadministered with RBT without dosage adjustment.
FAU - Ford, Susan L
AU  - Ford SL
AD  - GlaxoSmithKline, Research Triangle Park, NC, USA.
FAU - Lou, Yu
AU  - Lou Y
AD  - Parexel International, Research Triangle Park, NC, USA.
FAU - Lewis, Nicole
AU  - Lewis N
AD  - GlaxoSmithKline, Upper Providence, PA, USA.
FAU - Kostapanos, Michalis
AU  - Kostapanos M
AD  - Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, 
      Cambridge, UK.
AD  - GSK Clinical Unit Cambridge, Cambridge, UK.
FAU - D'Amico, Ronald
AU  - D'Amico R
AD  - ViiV Healthcare, Research Triangle Park, NC, USA.
FAU - Spreen, William
AU  - Spreen W
AD  - ViiV Healthcare, Research Triangle Park, NC, USA.
FAU - Patel, Parul
AU  - Patel P
AD  - ViiV Healthcare, Research Triangle Park, NC, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Pyridones)
RN  - 1W306TDA6S (Rifabutin)
RN  - HMH0132Z1Q (cabotegravir)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Anti-HIV Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Drug Interactions
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyridones/administration & dosage/adverse effects/*pharmacokinetics
MH  - Rifabutin/*pharmacology
MH  - Young Adult
EDAT- 2019/03/22 06:00
MHDA- 2020/07/01 06:00
CRDT- 2019/03/22 06:00
PHST- 2019/02/24 00:00 [accepted]
PHST- 2019/03/22 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2019/03/22 06:00 [entrez]
AID - 10.3851/IMP3306 [doi]
PST - ppublish
SO  - Antivir Ther. 2019;24(4):301-308. doi: 10.3851/IMP3306.